P533: SINGLE-CENTER PHASE 2 STUDY OF PD-1 INHIBITOR COMBINED WITH DNA DEMETHYLATION AGENT + CAG REGIMEN IN PATIENTS WITH HIGH-RISK ACUTE MYELOID LEUKEMIA: INTERIM ANALYSIS
Authors: X.-N. Gao, Y.-F. Su, Y. Jing, J. Wang, L. Xu, L.-L. Zhang, A. Wang, Y.-Z. Wang, Y.-F. Li, D.-H. Liu
Journal: HemaSphere (2022)

Background: The expression of PD-L1 is increased in acute myeloid leukemia (AML) cells. However, blocking the immune checkpoint alone has limited efficacy as a single agent in highly proliferative leukemia cells. Here we report the results of an interim analysis of an ongoing single-arm phase 2 trial (no. NCT04541277) of PD-1 inhibitor combined with DNA demethylation agent + CAG regimen in patients with high-risk AML. Aims: To assess safety and response to Tislelizumab + Azacytidine/Decitabine + CAG regimen after minimum 1 cycle of therapy in patients who failed at least one prior induction course of therapy or developed relapse (Cohort 1), and patients with persistent minimal residual disease (MRD)-positivity after consolidation treatment (Cohort 2). Methods: Patients must have failed at least one prior induction course of therapy or have a relapse or have a persistent MRD-positive disease after consolidation treatment. Other eligibility criteria included in ECOG performance status ≤ 2, normal organ function, and no autoimmune diseases requiring systemic immunosuppression. The patients received Azacytidine 75 mg/m2 subcutaneously daily, day 1-7 or Decitabine 20 mg/m2 intravenously daily, day 1-5 plus CAG regimen (cytarabine 100 mg intravenously every 12 hours, day 1-5; aclarubicin 20 mg intravenously daily, day 1-5; and concurrent use of G-CSF 5 mg/kg/day subcutaneously) with Tislelizumab 200 mg beginning on the next day after chemotherapy was stopped and every 4 weeks thereafter. This study was approved by the Ethics Committee of the Chinese PLA General Hospital, and signed informed consents were obtained from all patients. Results:Efficacy: Fifteen patients has been enrolled (Table 1). Fourteen (93.3%) are evaluable for response, 7 (46.7%) completed 2 cycles and 8 (53.3%) completed 1 cycle: Of the 12 patients in the previous treatment failure cohort, 7 achieved complete remission (CR)/CR with incomplete hematologic recovery (CRi) (1/7) (Table 1B), 3 partial remission (PR), and 2 non-remission. Of the 2 patients in the persistent MRD-positivity after consolidation treatment cohort, 1 achieved MRD negativity and 1 had no response. The 8-week mortality were 18.8%: 2 patients died of rapidly progressive disease concomitant with lung infection at 34 days and 56 days after treatment, respectively. One died of relapse of disease at +4 months after received HLA-haploidentical peripheral blood stem cell transplantation (PBSCT). One died of acute graft-versus-host disease of the gastrointestinal tract at +35 days after received a HLA-haploidentical PBSCT in NR status at transplant. With a median follow-up of 5.4 months (1.1 -12.7), the median overall survival (OS) is not reach with an estimated 1-yr OS of 59.6% (95%CI, 17.8%-85.6%). The median OS for responders (CR/CRi+PR) is not reach vs. 1.9 months for non-responders (p=0.083). The median event-free survival (EFS) is 6.5 months with an estimated 1-yr EFS of 58.3% (95%CI, 7.7%-89.3%). Toxicity: Grade 2 immune-related adverse events (IRAEs) were observed in 2 (13.3%) patients, included in 1 patient with grade 2 skin rash which resolved with steroids, and the other with grade 2 peripheral sensory neuropathy. All patients developed treatment-related grade 3 or 4 hematologic toxicities. Two patients died of lung infection at 34 days and 56 days after treatment in the setting of PD. Image:Summary/Conclusion: Tislelizumab + Azacytidine/Decitabine + CAG regimen is safe and effective for high-risk AML patients. IRAEs are mild, low-grade. Special attention needs to be paid to patients who have an increased risk of developing graft-versus-host disease.